臺灣博碩士論文加值系統

臺灣五葉松(Pinus morrisonicola Hay)已被證實具有抗氧化、抗發炎及降血脂能力。過去研究得知，五葉松針超臨界二氧化碳萃取物(PME3)再以薄層色層與管柱層析分離法所得之PME3-1比PME3更具有抗氧化及降血脂潛力，因此本研究乃更進一步探討PME3-1在活體內是否具有降血脂的能力及其可能機制。本實驗以高油脂、高膽固醇(15% Fat,0.2% Cholesterol)(HFC飲食)連續餵食8週齡倉鼠30天後，再開始連續餵食60天之PME3-1樣品(低、中及高劑量分別為0.2、1.0及5.0 mg/kg b.w)，期間並同時持續投與HFC飲食。研究結果顯示，餵食PME3-1可顯著抑制HFC飲食倉鼠之肝及腎臟的腫大(p<0.05)，並可使脾臟的重量回復至與空白組無顯著性差異(p>0.05)。在血清生化指標方面，餵食PME3-1倉鼠之血清膽固醇、三酸甘油酯、LDL/HDL比率均顯著低於控制組(p<0.05)，其抑制效果甚至顯著優於SIM組(5 mg/kg b.w 之Simvastatin) (p<0.05)。在肝、腎臟的組織病理切片中發現，PME3-1具有降低脂肪變性(fatty change)與慢性腎發炎(Chronic progressive nephrosis; CPN)的趨勢。另外，也發現高劑量PME3-1組可顯著降低高脂飲食倉鼠之肝臟中的總脂質、總膽固醇與總三酸甘油酯的含量，也能顯著降低肝臟中之HMG-CoA reductase活性(p<0.05)，也可顯著促進其糞便膽固醇及三酸甘油酯的排出(p<0.05)。在抗氧化能力評估方面，PME3-1在低劑量即可顯著降低肝臟中脂質過氧化物-Malondialdehyde (MDA)的形成，但只有高劑量組可顯著降低glutathione peroxidase (GPx)的活性(p<0.05)，對肝臟中superoxide dismutase (SOD)及Glutathione S-transferase (GST)等酵素活性則無顯著性影響(p>0.05)。綜合上述結果，PME3-1具有降低HFC飲食所誘導之血清高血脂及肝臟堆積脂肪的效果，並能抑制肝臟脂質過氧化物作用，而其降低血脂的可能機制推測與其能抑制肝臟膽固醇合成酵素HMG-CoA reductase的活性與促進腸道中脂質排出有關，未來應有應用於預防心臟血管疾病的潛力。

Taiwan's five-leaf pine (Pinus morrisonicola Hay; PM) has been shown to have antioxidant, anti-inflammatory and hypolipidemic potential. Past studies show that the antioxidant and hypolipidemic effects of supercritical CO2 extract refraction from PM needles purified by thin layer and column chromatography methods (PME3-1) is better than unrefracting of PME3. Therefore, the aim of this study was further to investigate the hypolipidemic effects of PME3-1 and its possible mechanisms in vivo. We fed a high-fat and high-cholesterol diet (15% Fat, 0.2% Cholesterol)(HFC diet) for 30 days before feeding PME3-1 (low, medium and high doses of 0.2, 1.0 and 5.0 mg/kg bw) in 8-weeks-old hamsters for 60 days, and continuous feeding HFC diet during the period. The results indicated that supplementation with PME3-1 can significantly inhibit the liver and kidney swelling and restore the spleen weight of hamster induced by HFC diet. There were no significant difference in liver, kidney and spleen weight of hamster when compare with those of blank group(p>0.05). In the serum biochemical parameter analysis, cholesterol, triglycerides and LDL/HDL ratios in PME3-1-treated hamster were all significantly lower than those of the HFC diet group (p<0.05), and the inhibitory effects of PME3-1 on the serum lipidemia parameter were even better than that of Simvastatin (5 mg/kg b.w) (p<0.05). Histopathological evaluation of the hamster liver and kidney revealed that PME3-1 reduced the incidence of fatty change in liver and chronic progressive nephrosis in kidney induced by HFC diet. In addition, it found that high doses of PME3-1 group can significantly reduce total lipids (TL), total cholesterol (TC) and total triglycerides (TG) and inhibit HMG-CoA reductase activity of liver (p<0.05), and significantly promote fecal TC and TG (p<0.05) excretion in HFC diet hamsters (p<0.05). In the antioxidant ability assessment, the results indicated that PME3-1 can significantly reduce lipid peroxides- malondialdehyde formation of liver at the low dose of PME3-1, however, only high-dose of PME3-1 can significantly reduce glutathione peroxidase activity (p<0.05). Furthermore, the other enzymes, such as superoxide dismutase and glutathione S-transferase of liver cannot be influence by PME3-1 in HFC diet hamster. Based above results, PME3-1 revealed the potent hypolipidemic effects and the inhibitory ability on lipid peroxidation of liver in HFC diet hamsters. Thus, we speculated that hypolipidemic effects of PME3-1 may be due to the inhibition of TC and TG synthesis and reduction of lipid peroxidation in the liver. We suggested that PME3-1may be useful for prevention of cardiovascular disease.

目錄

封面內頁
簽名頁
授權書.........................................................................................iii
中文摘要.....................................................................................v
英文摘要.....................................................................................vii
誌謝.............................................................................................ix
目錄............................................................................………….x
圖目錄 ........................................................................................xiv
表目錄 ........................................................................................xv
縮寫表(英文)……………………………………………………xvi
第一章 前言…………………...................................................1
第二章文獻回顧………………………………………………..5
2.1何謂高血脂症 5
2.1.1血脂質 7
2.1.1.1三酸甘油脂 8
2.1.1.2膽固醇 8
2.1.2脂蛋白 9
2.1.2.1乳糜微粒 10
2.1.2.2極低密度脂蛋白 10
2.1.2.3低密度脂蛋白 11
2.1.2.4中密度脂蛋白 12
2.1.2.5高密度脂蛋白 12
2.2高血脂及高膽固醇對人體健康的影響 12
2.3高血脂症治療方式 13
2.4降血脂及降膽固醇的食物成分 14
2.4.1紅麴類： 14
2.4.2大蒜萃取物： 15
2.4.3植物固醇類： 15
2.4.4水溶性膳食纖維： 16
2.5降血脂藥物 16
2.6降血脂的作用機制 17
2.6.1在抑制脂質及膽固醇的吸收部分： 17
2.6.2在抑制脂質及膽固醇合成部分： 17
2.6.2.1抑制膽固醇合成的路徑： 18
2.6.2.2抑制脂肪酸合成的路徑： 20
2.6.3促進脂質分解部分： 21
2.6.4抗氧化部分： 21
2.7超臨界流體萃取 22
2.7.1超臨界流體（Super Critical fluid, SCF）定義 22
2.7.2超臨界二氧化碳萃取技術的優點 23
2.8精油的製備方法 23
2.8.1精油相關之研究 25
2.8.1.1精油抗菌方面研究 26
2.8.1.2精油抗氧化方面研究 26
2.8.1.3精油降血脂方面研究 27
2.9台灣五葉松簡介 27
2.9.1五葉松的生長特性 28
2.9.2古籍之五葉松功效記載 28
2.9.3五葉松的機成性與機能性成分 29
2.9.3.1多酚類 (polyphenols) 30
2.9.3.2膳食纖維 (dietary fiber) 32
2.9.4五葉松的功能研究 33
2.9.4.1抗腫瘤之研究 33
2.9.4.2降血脂之研究 34
2.9.4.3抗氧化之研究 34
2.9.4.4降低總膽固醇之研究 35
第三章 材料與方法……………………………………………37
3.1實驗方法 37
3.1.1動物實驗設計 37
3.1.2材料 39
3.1.3樣品製備 40
3.1.4實驗設備 41
3.1.5血液及組織樣品之收集 41
3.2.分析項目 42
3.2.1 血漿中脂質的測定 42
3.2.2 肝臟中總脂質濃度之測定 42
3.2.3 肝臟及腎臟病理組織切片製作 44
3.2.4糞便膽固醇及三酸甘油酯測定 44
3.2.5 GSH S-transferase (GST)活性測定 44
3.2.6 GSH peroxidase (GPx)活性測定 45
3.2.7丙二醛（malondialdehyde, MDA）含量測定 45
3.2.8 HMG-CoA reductase測定 46
3.3 統計分析 46
第四章 結果…………………………………………………….47
4.1 PME3-1對HFC飲食倉鼠之體重影響 47
4.2 PME3-1對HFC飲食倉鼠之器官相對重量的影響 47
4.3 PME3-1對HFC飲食倉鼠之血清生化值的影響 48
4.4 PME3-1對HFC飲食倉鼠之肝臟損傷的影響 49
4.5 PME3-1對HFC飲食倉鼠之肝臟及糞便中脂質及膽固醇含量的影響 50
4.6 PME3-1對HFC倉鼠之肝臟中抗氧化狀態的影響 50
4.7 PME3-1對HFC飲食倉鼠之肝臟中HMG-COA reductas活性的影響 51
第五章 討論…………………………………………………….52
第六章 結論…………………………………………………….58
參考文獻………………………………………………………...67

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